单基因糖尿病遗传学研究进展：基因型–表型关联及精准诊疗新策略

Advances in Genetic Research on Monogenic Diabetes: Genotype-Phenotype Correlations and Novel Strategies for Precision Diagnosis and Treatment

摘要: 单基因糖尿病(Monogenic Diabetes)是一类由单个基因变异导致的特殊类型糖尿病，其发病机制与传统1型糖尿病和2型糖尿病存在显著差异。随着高通量测序技术的发展，越来越多与单基因糖尿病相关的致病基因被发现，使疾病诊断逐渐从临床表型驱动向分子遗传学驱动转变。与此同时，不同基因变异不仅影响疾病的发生，还在一定程度上决定患者的临床表型特征、疾病进展速度以及对药物治疗的反应差异。近年来，基因型–表型关联研究不断深入，使得单基因糖尿病的疾病谱系逐渐清晰，也为精准诊疗策略的建立提供了重要理论基础。本文系统综述在于阐述单基因糖尿病的遗传学基础、主要致病基因、基因型–表型关联特征、分子诊断技术及精准治疗策略，并对未来研究方向进行相关的展望，以期为临床诊疗与基础研究提供参考依据。

Abstract: Monogenic diabetes is a distinct subtype of diabetes caused by mutations in a single gene, with pathogenic mechanisms that differ significantly from those of classical type 1 and type 2 diabetes. With the advancement of high-throughput sequencing technologies, an increasing number of causative genes associated with monogenic diabetes have been identified, gradually shifting the diagnostic paradigm from a clinical phenotype-driven approach to a molecular genetics-based one. Moreover, different genetic variants not only influence disease onset but also, to a certain extent, determine patients’ clinical phenotypic characteristics, the rate of disease progression, and differential responses to pharmacological therapy. In recent years, in-depth investigations into genotype-phenotype correlations have progressively clarified the disease spectrum of monogenic diabetes and have provided a crucial theoretical foundation for the development of precision diagnostic and therapeutic strategies. This review systematically summarizes the genetic basis of monogenic diabetes, major causative genes, genotype-phenotype correlation features, molecular diagnostic techniques, and precision treatment approaches, and also offers perspectives on future research directions, aiming to serve as a reference for clinical practice and basic research.